Localized Inflammatory Response

The hallmarks of a localized acute inflammatory response, first described almost 2000 years ago, are swelling (tumor), redness (rubor), heat (calor), pain (dolor), and loss of function. Within minutes after tissue injury, there is an increase in vascular diameter (vasodilation), resulting in an increase in the volume of blood in the area and a reduction in the flow of blood. The increased blood volume heats the tissue and causes it to redden. Vascular permeability also increases, leading to leakage of fluid from the blood vessels, particularly at postcapillary venules. This results in an accumulation of fluid (edema) in the tissue and, in some instances, extravasation of leukocytes, contribut

VISUALIZING CONCEPTS

VISUALIZING CONCEPTS

Complement activation

Complement activation

Vascular Changes Acute Inflammation

Plasmin

FIGURE 15-12

Overview of the cells and mediators involved in a local acute inflammatory response. Tissue damage leads to the formation of complement products that act as opsonins, anaphyla-toxins, and chemotactic agents. Bradykinin and fibrinopeptides induced by endothelial damage mediate vascular changes. Neutrophils generally are the first leukocytes to migrate into the tissue, followed by monocytes and lymphocytes. Only some of the interactions involved in the extravasation of leukocytes are depicted.

Plasmin

Bradykinin Fibrin

Fibrinopeptides

FIGURE 15-12

Overview of the cells and mediators involved in a local acute inflammatory response. Tissue damage leads to the formation of complement products that act as opsonins, anaphyla-toxins, and chemotactic agents. Bradykinin and fibrinopeptides induced by endothelial damage mediate vascular changes. Neutrophils generally are the first leukocytes to migrate into the tissue, followed by monocytes and lymphocytes. Only some of the interactions involved in the extravasation of leukocytes are depicted.

ing to the swelling and redness in the area. When fluid exudes from the bloodstream, the kinin, clotting, and fibrinolytic systems are activated (see Figure 15-10). Many of the vascular changes that occur early in a local response are due to the direct effects of plasma enzyme mediators such as bradykinin and fib-rinopeptides, which induce vasodilation and increased vascular permeability. Some of the vascular changes are due to the indirect effects of the complement anaphylatoxins (C3a, C4a, and C5a), which induce local mast-cell degranulation with release of histamine. Histamine is a potent mediator of inflammation, causing vasodilation and smooth-muscle contraction. The prostaglandins can also contribute to the vasodilation and increased vascular permeability associated with the acute inflammatory response.

Within a few hours of the onset of these vascular changes, neutrophils adhere to the endothelial cells, and migrate out of the blood into the tissue spaces (Figure 15-12). These neutrophils phagocytose invading pathogens and release mediators that contribute to the inflammatory response. Among the mediators are the macrophage inflammatory proteins (MIP-1a and MIP-1p), chemokines that attract macrophages to the site of inflammation. Macrophages arrive about 5-6 hours after an inflammatory response begins. These macrophages are activated cells that exhibit increased phagocytosis and increased release of mediators and cyto-kines that contribute to the inflammatory response.

Activated tissue macrophages secrete three cytokines (IL-1, IL-6, and TNF-a) that induce many of the localized and systemic changes observed in the acute inflammatory response (see Table 15-3). All three cytokines act locally, inducing coagulation and an increase in vascular permeability. Both TNF-a and IL-1 induce increased expression of adhesion molecules on vascular endothelial cells. For instance, TNF-a stimulates expression of E-selectin, an endo-thelial adhesion molecule that selectively binds adhesion molecules on neutrophils. IL-1 induces increased expression of ICAM-1 and VCAM-1, which bind to integrins on lymphocytes and monocytes. Circulating neutrophils, monocytes, and lymphocytes recognize these adhesion molecules on the walls of blood vessels, adhere, and then move through the vessel wall into the tissue spaces. IL-1 and TNF-a also act on macrophages and endothelial cells to induce production of the chemokines that contribute to the influx of neutro-phils by increasing their adhesion to vascular endothelial cells and by acting as potent chemotactic factors. In addition, IFN-7 and TNF-a activate macrophages and neutrophils, promoting increased phagocytic activity and increased release of lytic enzymes into the tissue spaces.

A local acute inflammatory response can occur without the overt involvement of the immune system. Often, however, cytokines released at the site of inflammation facilitate both the adherence of immune-system cells to vascular en-dothelial cells and their migration through the vessel wall into the tissue spaces. The result is an influx of lymphocytes, neutrophils, monocytes, eosinophils, basophils, and mast cells to the site of tissue damage, where these cells participate in clearance of the antigen and healing of the tissue.

The duration and intensity of the local acute inflammatory response must be carefully regulated to control tissue damage and facilitate the tissue-repair mechanisms that are necessary for healing. TGF-p has been shown to play an important role in limiting the inflammatory response. It also promotes accumulation and proliferation of fibroblasts and the deposition of an extracellular matrix that is required for proper tissue repair.

Clearly, the processes of leukocyte adhesion are of great importance in the inflammatory response. A failure of proper leukocyte adhesion can result in disease, as exemplified by leukocyte-adhesion deficiency (see Clinical Focus on page 358).

Essentials of Human Physiology

Essentials of Human Physiology

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Responses

  • jaime
    What steps occur in an acute inflammatory response?
    7 years ago
  • tamzin murray
    What causes these changes in the inflammatory response (redness, localized heat, edema, and pain)?
    6 years ago
  • petra
    What are three vascular changes that occur early in the inflammatory responce?
    5 years ago
  • basso trentini
    What triggers localized inflmatory response?
    3 years ago
  • largo
    Why inflammatory response causes vasodilation?
    11 months ago
  • juuso
    Which of the following promotes localized inflammation?
    7 months ago

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